Ultrasound transducer and uses thereof

ABSTRACT

According to some embodiments there is provided a method for controlling a treatment effect on blood vessel tissue during an ultrasonic treatment, the method comprising positioning an ultrasonic transducer device in the blood vessel lumen; controlling a treatment effect by controlling fluid flow, wherein controlling comprises deploying a fluid restrictor at a location relative to the transducer effective to block at least a portion of fluid flowing upstream, downstream or adjacent the transducer. According to some embodiments there is provided an ultrasonic transducer device sized for placement in a body lumen, and comprising a fluid restrictor effective to block at least a portion of fluid flowing upstream, downstream or adjacent the transducer. In some embodiments, the fluid is blood.

RELATIONSHIP TO EXISTING APPLICATIONS

This application is a division of U.S. patent application Ser. No.13/049,013 filed Mar. 16, 2011, which claims the benefit of priorityunder 35 USC 119(e) of U.S. Provisional Patent Application No.61/393,947 filed Oct. 18, 2010. The contents of the above applicationsare all incorporated by reference as if fully set forth herein in theirentirety.

FIELD AND BACKGROUND OF THE INVENTION

The present invention relates to an ultrasound transducer device anduses thereof and, more particularly, but not exclusively to such atransducer device modified for use in surgical procedures.

Sverdlik et al, in PCT/IL2008/000234, filed Feb. 21, 2008 disclose amethod of using ultrasonic energy for surgical procedures. In aprocedure for stabilizing blood vessel wall abnormality, ultrasonicheating is carried out of at least a portion of the blood vessel wallhaving the abnormality. A parameter is monitored relating to a propertyof at least a portion of the heated portion of the blood vessel wall;and heating is stopped when the monitored parameter changes by apredetermined factor or after the monitored parameter changes at a slowenough rate.

A problem arises in providing the ultrasound transducer close to thetissue that requires the procedure. It is known to put small ultrasoundsensors in the blood vessels but it is difficult to ensure that thesensor is looking at the tissue that requires the procedure. A furtherproblem involves providing the ultrasound power beam sufficiently closeto the tissue requiring ablation, and controlling the beam given a) thedifficulty in correctly directing the sensor and b) generallycontrolling factors that affect efficiency of the ablation beam.

SUMMARY OF THE INVENTION

The present embodiments may provide a transducer in which sensing andablation are combined on a single transducer device that can be placedin a blood vessel or the like.

According to one aspect of the present invention there is provided adual use ultrasonic transducer device for combined sensing and powertransmission, the power transmission for tissue ablation, comprising:

a first piezoelectric transducer sized for placement in a body lumen;

a power unit enabling an ultrasonic power beam for tissue ablation in atissue ablation region; and

a sensing unit enabling an ultrasonic sensing beam for sensing at saidtissue ablation region.

In an embodiment, said first piezoelectric transducer comprises apiezoelectric surface, said piezoelectric surface being electricallyconnected to a mounting; the mounting comprising damping for saidpiezoelectric surface, the mounting being configured such as to providea first region of said piezoelectric surface with a first relativelyhigh level of damping and a second region of said piezoelectric surfacewith a second relatively low level of damping, thereby to enable saidultrasonic sensing beam from said first region and said powertransmission beam from said second region.

An embodiment may comprise at least a second piezoelectric transduceralso sized for placement in a body lumen, the first piezoelectrictransducer being provided with a first, relatively high level of dampingand the second piezoelectric transducer being provided with a second,relatively low, level of damping, and enabling said ultrasonic sensingbeam from said first piezoelectric transducer and said ultrasonic powerbeam from said second piezoelectric transducer.

In an embodiment, said ultrasonic power beam and said ultrasonic sensingbeam are enabled through said first piezoelectric transducer.

In an embodiment, said body lumen is a blood vessel.

An embodiment may comprise with a catheter for placing within said bloodvessel.

In an embodiment, said sensing is usable in a control system to controltreatment efficacy or device efficiency.

In an embodiment, said first piezoelectric transducer is configured toprovide said power transmission as a non-focused beam.

In an embodiment, said first region comprises a first surface part ofsaid piezoelectric surface and said second region comprises a secondsurface part of said piezoelectric surface, and a non-focused beam isprovided from throughout said second surface part.

In an embodiment, said power transmission is configured to provide athermal effect to surrounding tissues and said sensing is configured toprovide imaging of said thermal effect.

In an embodiment, said thermal effect comprises denaturation of collagenand said sensing comprises detection of a change in reflected signal, orin backscatter.

An embodiment may provide said power transmission in bursts having gapsand transmit separate sensing transmissions during said gaps.

An embodiment is configured to be placed in said body lumen and saidsensing region is configured to detect a lumen wall and to provide asignal to control for distance to the lumen wall and thereby ensure thatthe device does not touch said lumen wall.

In an embodiment, said mounting comprises an air pocket and a pluralityof contact points.

In an embodiment, said mounting is provided with a surface tensionsufficient to maintain said air pocket when said device is immersed inliquid.

An embodiment may comprise a matching layer for acoustic impedancematching placed on said piezoelectric surface wherein said matchinglayer comprises pyrolytic graphite.

The device may have a resonance and an anti-resonance, and mayadvantageously be used at a working frequency equal to saidanti-resonance.

According to a second aspect of the present invention there is provideda method of online testing of efficiency or treatment efficacy of anultrasound transducer to detect changes in said efficiency, saidefficiency being a ratio between ultrasound energy and heat generated insaid transducer, said method comprising applying an impulse to saidultrasound transducer, measuring a response of said ultrasoundtransducer to said impulse, and inferring changes in said efficiency orsaid efficacy from said measured response.

In an embodiment, said inferring said changes in efficiency comprisesinferring from at least one member of the group comprising: a shape ofsaid measured response; an envelope of said measured response, aduration of said measured response, amplitudes of said measuredresponse, and a damping factor of said measured response.

In an embodiment, said transducer has a resonance and an anti-resonanceand said online or offline testing comprises inferring a change in atleast one of said resonance and said anti-resonance.

Usage of the embodiment may involve placing said transducer in aliquid-filled body lumen and carrying out said online testing while saidtransducer is in said body lumen.

The embodiments extend to the device when placed in a liquid within abody lumen.

According to a third aspect of the present invention there is provided amethod of using an ultrasonic transducer for simultaneous heating andmonitoring of a target, the method comprising providing a relativelyhigh power ultrasonic transmission in bursts for heating said target,said bursts having gaps, and sending relatively low power ultrasonicsensing transmissions during said gaps for monitoring said target.

An embodiment may comprise using a surface of a piezoelectric sensor toproduce said relatively high power and said relatively low powerultrasonic transmissions, said piezoelectric sensor surface comprising afirst relatively high damping region and a second relatively low dampingregion, the method comprising using said first region for saidmonitoring and said second region for said heating.

An embodiment may comprise placing said transducer in a liquid-filledbody lumen and carrying out said simultaneous heating and measuringwhile said transducer is in said body lumen.

An embodiment may involve testing an efficiency of said transducer or atreatment efficacy, said testing comprising applying an impulse to saidtransducer and measuring a response of said transducer to said impulse.

According to a fourth aspect of the present invention there is provideda method of online testing of efficiency of an ultrasound transducer todetect changes in said efficiency, said efficiency being a ratio betweenultrasound energy and heat generated in said transducer, said methodcomprising measuring an impedance of said transducer at a currentworking frequency, and inferring changes in said efficiency from changesin said measured impedance.

According to a fifth aspect of the present invention there is provided amethod of online testing of efficiency of an ultrasound transducer todetect changes in said efficiency, said efficiency being a ratio betweenultrasound energy and heat generated in said transducer, or for testingtreatment efficacy, said transducer being for placement in a liquid flowand having a temperature sensor positioned for measurement of flowingliquid downstream of said transducer, said method comprising measuring atemperature of said flowing liquid downstream of said transducer, andinferring a decrease in said efficiency or a change in said efficacyfrom an increase in said measured temperature.

According to a sixth aspect of the present invention there is provided amethod of online testing of treatment efficacy and safety of the deviceof claim 1, comprising placing the device in said lumen at a distancefrom a lumen wall, measuring liquid flow between the device and the walland using changes in said flow measurement as an indicator of saidtreatment efficacy or said safety.

Unless otherwise defined, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention belongs. The materials, methods, andexamples provided herein are illustrative only and not intended to belimiting.

The word “exemplary” is used herein to mean “serving as an example,instance or illustration”. Any embodiment described as “exemplary” isnot necessarily to be construed as preferred or advantageous over otherembodiments and/or to exclude the incorporation of features from otherembodiments.

The word “optionally” is used herein to mean “is provided in someembodiments and not provided in other embodiments”. Any particularembodiment of the invention may include a plurality of “optional”features unless such features conflict.

Implementation of the method and/or system of embodiments of theinvention can involve performing or completing selected tasks manually,automatically, or a combination thereof. This refers in particular totasks involving control of the ultrasonic system.

Moreover, according to actual instrumentation and equipment ofembodiments of the method and/or system of the invention, selected tasksmay be implemented by hardware, by software or by firmware or by acombination thereof using an operating system.

For example, hardware for performing selected tasks according toembodiments of the invention may be implemented as a chip or a circuit.As software, selected tasks according to embodiments of the inventioncould be implemented as a plurality of software instructions beingexecuted by a computer using any suitable operating system. In anexemplary embodiment of the invention, one or more tasks according toexemplary embodiments of method and/or system as described herein areperformed by a data processor, such as a computing platform forexecuting a plurality of instructions. Optionally, the data processorincludes a volatile memory for storing instructions and/or data and/or anon-volatile storage, for example, a magnetic hard-disk and/or removablemedia, for storing instructions and/or data. Optionally, a networkconnection is provided as well. A display and/or a user input devicesuch as a keyboard or mouse are optionally provided as well.

BRIEF DESCRIPTION OF THE DRAWINGS

The patent or application file contains at least one drawing executed incolor. Copies of this patent or patent application publication withcolor drawing(s) will be provided by the Office upon request and paymentof the necessary fee.

The invention is herein described, by way of example only, withreference to the accompanying drawings. With specific reference now tothe drawings in detail, it is stressed that the particulars shown are byway of example and for purposes of illustrative discussion of thepreferred embodiments of the present invention only, and are presentedin order to provide what is believed to be the most useful and readilyunderstood description of the principles and conceptual aspects of theinvention. In this regard, no attempt is made to show structural detailsof the invention in more detail than is necessary for a fundamentalunderstanding of the invention, the description taken with the drawingsmaking apparent to those skilled in the art how the several forms of theinvention may be embodied in practice.

In the drawings:

FIG. 1 is a simplified schematic diagram of a first embodiment of anultrasound transducer in which sensing and ablation are combined onto asingle device according to the present invention;

FIG. 2 is a simplified schematic diagram showing a modification of thetransducer of FIG. 1;

FIG. 3A is a simplified flow chart illustrating a method for monitoringoperation of an ultrasound transducer according to embodiments of thepresent invention;

FIG. 3B is a flow chart showing a method of monitoring efficacy oroperation of an ultrasound transducer according to further embodimentsof the present invention;

FIG. 4 is a simplified flow chart illustrating a method for ablatingtissue using high power pulses, and measuring during gaps in the pulse,according to embodiments of the present invention;

FIG. 5 is a simplified schematic diagram of a system using theair-backed ultrasound transducer of FIG. 1;

FIG. 6 is a simplified schematic diagram showing a cross-section of theconstruction of an ultrasound transducer according to the embodiment ofFIG. 1;

FIGS. 7A-7C are simplified schematic diagrams illustrating variantshapes of a piezoelectric element for the transducer of FIG. 1;

FIG. 8A is a side view of a series of piezoelectric elements mounted ona single mounting according to an embodiment of the present invention;

FIG. 8B is a view from above of an arrangement of piezoelectric elementsmounted in two rows according to embodiments of the present invention;

FIG. 9 is a simplified schematic diagram illustrating a construction ofa PCB for mounting PCB elements that includes grooves for air bubbleformation according to an embodiment of the present invention;

FIG. 10 is a simplified schematic diagram that illustrates a series ofangles and positions in relation to a body vessel and a catheter, inwhich the transducer can be placed by navigation;

FIG. 11 is a histology slide using H&E stain, and showing the thermaleffect in a pig carotid artery;

FIG. 12 is a histology slide using H&E stain, and showing the thermaleffect in a pig renal artery;

FIG. 13 is a histology slide wherein analysis and marking of the thermaldamage area to a pig Carotid Artery is made by a trained pathologist;

FIG. 14 is a histology slide wherein analysis and marking of the thermaldamage area to a pig Renal Artery is made by a trained pathologist;

FIG. 15 is a histology slide showing analysis and marking of the blockedVasa-Vasorum, with arrows placed by a trained pathologist in a pigCarotid Artery Vasa-Vasorum in the adventitia; and

FIG. 16 shows two histology slides with analysis and marking of thethermal damage, or nerve degeneration area, made by trained pathologist,for a pig renal artery, and nerves in adventitia.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present embodiments comprise an ultrasound transducer device anduses thereof and, more particularly, but not exclusively, such atransducer device modified for use in surgical procedures. Thetransducer device combines imaging and ablation into a single device.

The single device may include multiple transducers or a singletransducer having multiple regions. The regions may provide respectivepower beams and measuring beams and methods are provided for estimatingchanges in efficiency while in use.

The principles and operation of an apparatus and method according to thepresent invention may be better understood with reference to thedrawings and accompanying description.

Before explaining at least one embodiment of the invention in detail, itis to be understood that the invention is not limited in its applicationto the details of construction and the arrangement of the components setforth in the following description or illustrated in the drawings. Theinvention is capable of other embodiments or of being practiced orcarried out in various ways. Also, it is to be understood that thephraseology and terminology employed herein is for the purpose ofdescription and should not be regarded as limiting.

Reference is now made to FIG. 1, which is a simplified diagram showing adual use ultrasonic transducer device 10 for combined sensing and powertransmission. The transducer comprises a piezoelectric surface 12 of apiezoelectric element. The element is mounted using mounting points 14to a printed circuit board 16. The combination of the PCB 16 and themounting points 14 form a mounting.

The piezoelectric element is electrically connected to the printedcircuit board. For example the mounting points may be comprised ofconductive glue, or may include wire connections. The piezoelectricelement is vibrated in use by the electrical input to transmit a beamand also vibrates in the presence of a beam to sense ultrasound echoes.Thus the mounting comprises damping for the piezoelectric element inorder to manage the vibrations. The mounting may provide differentlevels of damping to various parts of the piezoelectric element so as toprovide different regions on the surface which are distinguished bytheir different levels of damping. A highly damped region is good forsensing since an acoustic beam can be transmitted and the returning echocan be reliably read by a surface whose vibrations have already dieddown. On the other hand power transmission benefits from the vibrationsmounting up so that an undamped surface may be considered, and on thecontrary, a mounting that actually multiplies vibrations would bebetter.

Thus the embodiment of FIG. 1 may provide the two different levels ofdamping to two different parts of the surface, shown as 18 for thehighly damped low power sensing region and 20 for the low damping highpower transmission region, so that one part is optimized for powertransmission and the other part is optimized for sensing. The tworegions are connected using different electrodes so that their operationis kept separate.

The low damped, high power region 20 may be configured to provide thepower transmission as a non-focused beam.

The non-focused beam may be provided from throughout the surface part20, that is to say from throughout the body of the low damping highpower region.

The power beam may provide a thermal effect to surrounding tissues, thuscarrying out ablation. Different parts of the surrounding tissues mayhave different sensitivities to the non-focused power beam. The sensingmay provide imaging of the heating effect. Since, in the presentembodiment, the surface doing the imaging is an extension of the surfaceproviding the power beam, the sensing surface is necessarily correctlydirected for sensing.

In an alternative embodiment, the same sensor surface may be used forboth the power and imaging.

In a third embodiment different transducers may be placed on the device.Each transducer produces either a power beam or a measuring beam.Example configurations are shown below in FIGS. 8A and 8B.

The thermal effect that is used may comprise denaturation of collagen.The sensing may specifically involve detection of an increase inamplitude of the ultrasonic reflection over the transmitted beam, whichincrease in amplitude is an indicator of the denaturation of thecollagen.

The power beam may be transmitted in bursts. The gaps in between thebursts may then be used to transmit separate sensing transmissions atlower power and allow detection without interference from the powerbeam.

The device is designed to be placed in a body lumen. The sensing regionmay detect the wall of the lumen, and this can be used to provide asignal that can be used in a control loop to control for distance to thelumen wall. The control loop can thus be used to ensure that the devicedoes not touch the lumen wall.

The body lumen is generally liquid. The mounting, as discussed, includesgaps 26 between the contact points 14. The device may be designed sothat gaps remain air filled even when the device is in the lumen. Thusthe gaps 26 become air pockets which lie between the multiple contactpoints 14.

Reference is now made to FIG. 2 which is a variation of the device ofFIG. 1.

As discussed, the air pocket may be maintained by surface tension. Themounting may be designed with a surface tension sufficient to maintainthe air pocket when the device is immersed in liquid, and this may bedue to the materials themselves, or, if not sufficient, then suitablecoatings 22 and 24 may be applied.

In an embodiment, a matching layer 28, for acoustic impedance matching,may be placed on the piezoelectric surface 20. A suitable material forthe matching layer is pyrolytic graphite, due to its combination of heatconducting ability and biological compatibility. Specifically pyrolyticgraphite has little effect on platelets and thus does not increase therisk of clot formation.

In operation, electrical waves are applied to the acoustic surfaces 18and 20, which causes the surfaces to vibrate. The surfaces have resonantand anti-resonant frequencies, and the working frequency at which thedevice is typically operated is an anti-resonance. The anti-resonancewas found empirically to provide a highest efficiency in terms of aratio of conversion of electrical energy to sound as opposed toconversion of electrical energy to heat.

Reference is now made to FIG. 3A, which is a simplified flow diagramillustrating a method for monitoring operation of the transducer inorder to control efficiency of the device of the present embodiments, orto control efficacy of the treatment, as will be explained hereinbelow.The device efficiency may change during use, typically leading to adanger of overheating. The problem is believed to lie with materialsfrom the blood stream, particularly clots, getting attached to thedevice and changing the vibration dynamics. The anti-resonant frequencychanges as a result but, unless this is detected, the device continuesto work at the predefined working frequency. Thus the efficiency dropsand the device heats up.

To help solve the above problem the present embodiments may provide away of online testing of efficiency of the ultrasound transducer todetect changes in its efficiency. As mentioned above, the efficiency isa ratio between ultrasound energy and heat generated in the transducer.As shown in FIG. 3, the method involves applying an impulse to theultrasound transducer—box 30, and then measuring a response of theultrasound transducer to the impulse, as shown in box 32. Changes in aproperty of the response may then be used in decision box 34 to inferchanges in the efficiency of the device.

If such changes are detected then in box 36 an action is taken. Theaction may be stopping of the device. Alternatively it may involvechanging the applied duty cycle and/or the applied power oralternatively the change may involve modifying the working frequency ofthe device. Subsequently, the efficiency is tested again so that thedevice can rapidly converge on a new efficient working frequency. If nochanges are detected then a delay 38 may be introduced and the testrepeated.

The test may be carried out continuously during use.

In the test, the changes in efficiency can be inferred from a change ina property of the impulse response, as shown in FIG. 3A. Howeveralternatives for the test include scanning the device impedance againstfrequency, measuring the applied power and measuring the impedanceduring a pulse.

In the case of the impulse test, the property may be a shape or envelopeof the measured response. Alternatively the property may be a durationof the measured response, typically the time the response falls to apredetermined minimal threshold. The property may alternatively be anamplitude of the measured response, and as a further alternative theproperty may a damping factor, which is derived from the measuredresponse.

As described above, the transducer device has both a resonance and ananti-resonance. Indeed the device may have several resonant frequenciesand several anti-resonances formed from local maxima on the efficiencygraph. The online testing may involve inferring changes in any of thesemaxima and minima and thus in either a resonance or an anti-resonance.

The efficiency testing is a form of test which can be carried out insitu in the liquid-filled body lumen since the impulse response can bemonitored remotely via the contact points 14.

As an alternative, the impedance of the transducer device can be tested.A fall of say ten percent in the impedance can be taken as a signal tomove the working frequency or to stop the treatment.

Reference is now made to FIG. 3B, which is a simplified diagramillustrating a more detailed control loop for the transducer device. InFIG. 3B, changes in power, current, voltage, impedance, and temperatureare used together or as alternatives and changes are looked for. In thecase of current, voltage, and impedance, changes of 10 percent arelooked for. In the case of temperature a measurement in excess of 43degrees is looked for. A pulse cycle using a given power P at a dutycycle of D % is applied and over excitation leads to the devicestopping. Blood flow and acoustic feedback are also obtained.

Returning now to FIG. 2, and the ultrasonic transducer device, may havean acoustic matching layer 26 comprising pyrolytic graphite asdiscussed. The matching layer has a thickness 40, which isadvantageously a quarter of a wavelength of the power beam transmittedby the ultrasonic transducer. As mentioned the working frequency couldbe the anti-resonance of the device so that the thickness 40 is aquarter of a wavelength of the working frequency.

Reference is now made to FIG. 4, which illustrates a method of using anultrasonic transducer of the present embodiments for simultaneousheating and monitoring of a target. The method comprises a box 50 forproviding a relatively high power ultrasonic transmission in bursts forheating the target. The bursts have gaps, as discussed above, and themethod uses the gaps to send relatively low power ultrasonic sensingtransmissions—box 52—for monitoring the target. The measurements arethen read—box 54. As discussed, the high power and low power beams maybe provided from different parts of the same surface of a piezoelectricsensor which are differentially damped, at working frequencies which areanti-resonances of the transducer. Alternatively they may be providedfrom the same surface. Alternatively high power and low power beams maybe provided from different transducers on the device.

The present embodiments are now considered in greater detail. Thepresent embodiments relate generally to devices, parameters and methodsfor the treatment of tissue using ultrasonic waves in particular forheating, at a target area such as in the wall of a tube or cavity,located in the living body, The treatment may involve excitation usinghigh power acoustic energy.

The ultrasonic effect is achieved in such a way that there is controlover the heated target tissue volume and location. Preferably, acontrolled volume of tissue between the ultrasonic element and thetarget tissue, is not treated. This distal effect may be achievedwithout the need of mechanical contact with the cavity walls.

Detailed application of the above includes the ability to cause moderatethermal damage within a controlled volume at the outer side of a cavitywall without damaging the inner side of the vessel, the inner sideincluding different types of epithelium.

The treatment method may be applied by creating a gradient of differenttemperatures in the tissue by the combined effects of: heating thetissue with high power ultrasound and cooling of the tissue usingconduction and convection. The convection could be of natural fluid, forexample blood flow, or by artificial injection of cooling liquid, forexample cold saline injection. Additional temperature effects that arewidely elaborated in other sources may also simultaneously influence thetemperature gradient, for example—capillary blood perfusion.

The heating control is performed by controlling the parameters of theultrasonic field and the transmission protocol, including: transmissionfrequency, power, duration and duty cycle, as will be described ingreater detail herein.

The treatment is controlled by feedback from the tissue using an echoreceived from the tissue during the treatment. Specifically, at hightemperatures above 55° C. an irreversible change is created in thecollagen fibers in the tissue; this change may be monitored using theultrasonic echo from the tissue, which allows mapping of the damagedtissue area.

It is also possible to increase or\and to add effects by ejection offluids into the treated area or at an upstream area in such a way thatthe ejected fluid is inserted into the vessel, typically through thevasa-vasorum or the adventitia lymph capillary.

Nevertheless, it is possible to control the flow in the vessel atdifferent locations using different devices, for example a balloonopening in the vessel and again changing the treated effects in thetissue.

Typically, the ultrasonic transmission is applied at high power, highfrequency and for more than one second. Heating of the tissue in theultrasonic field is performed by absorption of the acoustic energy in aprocess of dissipation of mechanical energy. The absorption andinfluence of the energy on the tissue includes inter alia the followingeffects: a heating effect, a mechanical effect, a pressure effect, asub-pressure and a cavitation effect.

Simultaneously with the transmission the cooling effect is achieved byliquid flow in the vessel or fluid present (for example urine, lymphaticliquid, bile) or liquid active ejection.

The present embodiments may provide the possibility of transmitting theenergy without touching the cavity all. By not touching it is possibleto increase protection for both the elements and the non target tissueby allowing fluid to flow on the cavity walls and on the transducersurface. The liquid provides for cooling. The present embodiments mayalso allow for easier operation by not restricting the transducerlocation.

The present embodiments may transmit a non-focused acoustic field toreach the target tissue. An advantage of not having to focus the fieldis that there is no need to control the tissue distance from thetransducer. For example renal denervation may be carried out simply byallowing the catheter to transmit a wide, high power acoustic field froma nonspecific location in the artery to a distal nonspecific location ofthe renal nerve.

Embodiments of the invention may allow ejection of materials into thetreated area or to an upstream area therefrom in a way that thematerials are inserted into the vessel, say through the vasa-vasorum orthe adventitia lymph capillary.

The embodiments described herein allow sampling of the voltage createdon the ultrasonic element due to echoes from the tissue and processingthe data in such a way that the treated tissue is monitored.

Echoe sampling and recording and or processing for measurement andmonitoring can be performed simultaneously with the treatment. Suchsimultaneous treatment and analysis can increase the level of control ofthe treatment in real time and help ensure achievement of the desiredresults.

More specifically, the following information may be monitored from theechoes received within a vessel:

wall distance from the transducer,

vessel layer (media, adventitia, peri-adventitia) position,

thermal effect in the tissue location and

area of the thermal effect.

The data analysis method may include echo intensity, backscatter,spectral signature mapping, elastography, classification according toclassification matrix of tissues, and the ultrasonic effect.

The control unit may use the above data and analysis for increasing thetreatment, or reducing the treatment, or stopping the treatment, orproviding indications regarding the treatment stage, or providingindications to stop or to continue the treatment.

A therapeutic catheter with an ultrasonic transducer may allow fortransmission to the vessel from the inner side.

An ultrasonic transducer may be placed on the skin, with an internalcatheter and transmission to the outer side of the cavity.

An endoscope system may include an ultrasonic element in its tip. Theendoscope may be inserted through the skin and ultrasonic transmissionmay be provided to the outer side of the cavity.

The fluid control methods may include one or more of the followingimplementations:

A restrictor around the transducer. The implementation may involve:placing the transducer at a different location in the vessel, andcontrolling the flow;

A restrictor near the transducer. The implementation may again involveplacing the transducer at a different location in the vessel, andcontrolling the flow;

A restrictor in front of (upstream of) the transducer. The method mayinvolve blocking the flow upstream in order to load the vasa-vasorumwith liquid and particles.

A restrictor past, that is downstream of, the transducer. The method mayinvolve blocking the flow downstream of the transducer to allow drugdelivery specifically to the treated area;

The restrictor may be one or more of the following: a balloon, a wire,nets, or a thin plastic sheet.

Manipulation of in the tissue reaction to the ultrasonic treatment ispossible by:

Injecting vasoconstriction materials into the blood, and in this wayreducing the perfusion and heat evacuation from the tissue, or injectingor evoking micro-bubbles and increasing the heating by increasingabsorption of the ultrasonic energy, or the evoked micro-bubbles may beproduced by use of an additional separate transducer.

Micro-bubble transportation through the cell membrane may be increasedusing the acoustic treatment, and may achieve a multiplied effect.

The tissue may be cooled before treatment in order to protect and orcontrol the treated area and non-treated area.

Artificial opening of a minimal cavity surgery opening in the skin forinsertion of the therapeutic catheter may be provided.

The ultrasonic field and/or the level of perfusion can be controlled andmanipulated by influencing the body system in general.

Possible target tissues for the device include one or more of thefollowing and their nearby tissues to douse cavities: arteries, veins,lymph vessels, intestine, esophagus, CNS, urine lumen, gall lumen,Stomach, and Tear Trough.

Applications for the above-described embodiments include the following:

Blood vessel wall pathology. For example for an atherosclerotic lesion;

Healthy blood vessel wall treatment;

Treatment of tissue near the blood vessel wall, for example renaldenervation;

Treatment of tissue near the urine lumen wall, for example prostatetreatment;

Treatment of tissue far from the urine lumen wall, for example prostatecancer.

More detailed examples for treatment and advantages using the presentembodiments include phantom pain treatment in which, the target tissueis nerve tissue in the limbs. The catheter cavity may be located in alimb artery. The purpose of the treatment may be reducing phantom paininnervations by denerving the injured nerve.

A point to note is that the attenuation of the ultrasound field issmaller in the fatty tissue around the nerves than in the nervesthemselves at the device frequencies. Furthermore the fatty tissue, dueto its low heat conduction, isolates the heat created in the nerves.Such phenomena increase the selectiveness of the treatment.

An additional example of treatment is renal denervation.

In this treatment the target is the renal nerves. The catheter cavity islocated in the renal artery. The purpose is to reduce pressure on theheart for high blood pressure patients. It is noted that the frequency,power and acoustic beam as per the data and results hereinbelow, treatthe nerves without or with minimal damage to the artery. In addition, asin the previous example, the attenuation is smaller in the fatty tissuearound the nerves than in the nerves themselves at the devicefrequencies, which increases the selectiveness of the treatment.

Possible treatment effects in the tissues can be one or more of thefollowing:

Cell necrosis occurring in one or more of: lymphocytes, macrophages,smooth muscle cells, fibroblasts, endothelial cells, and neurons;

Reduced change in the tissue activity including: reducing smooth musclefunction, reducing or blocking nerve activity, reducing or blocking thegeneration of the heart beat potential to the heart muscles;

Mechanical blocking of the vasa-vasorum or\ and the lymph capillary;

Mechanical changes in the collagen fibers, an increase or decrease instiffness and reducing the maximal tension for tearing;

Biochemical changing in the tissues may include: reducing or preventingplate connection to collagen, and changes of material diffusion throughthe cell walls.

The device may be operated using typical parameters for acoustictransmission as follows:

Transmission frequency: 5-30 MHz;

imaging frequency 5-60 MHz;

Transmission intensity (SATA): up to 200 w/cm²;

Transmission duration (total time): 1-120 seconds.

Reference is now made to FIG. 5, which is a simplified block diagram ofa system according to an embodiment of the present invention. In FIG. 5,the system 110 may contain one or more of an acoustic transducer 112, apower supply unit 114, a control unit 116, a pumping or circulationunit, shown as perfusion unit 118, a balloon control unit 120, and anavigating shaft 122.

The navigating unit allows the acoustic element to navigate to thelocation or locations at which it is needed. The balloon control unitcontrols a balloon for supporting the lumen as needed. The perfusionunit provides injection substances as necessary.

Reference is now made to FIG. 6, which is a schematic illustration ofthe acoustic element 112 of FIG. 1. The acoustic element 112, typicallyan ultrasonic element, includes a piezoelectric element 124 whichconverts electrical energy into an acoustic beam. The piezoelectricelement is mounted on PCB board 126, for example via air gap 128. ThePCB in turn is mounted on housing 130 which protects the acousticelement.

The ultrasonic elements transfer the energy to the target tissue, andmay also be used as sensors for receiving reflections from the tissue.

The ultrasonic element may also be used as a jet evacuator of fluids forcooling or/and for drug delivery.

The ultrasonic element can be used as a microbubble evacuator.

The ultrasonic element typically includes one or more ultrasonictransducers including a piezoelectric material 24 or a MEMS element.

Electrodes may provide power to the transducer. The housing 30 protectsthe assembly, and an electrical connection may be provided between theelectrodes and the catheter wires.

The transducer element 124 may, as mentioned by a piezo-electricelements or a MEMS element.

A PIEZO-electric transducer element may typically be made fromPIEZO-electric material, for example: PZT ceramics, PIEZO-electricquartz.

Reference is now made to FIGS. 7A, 7B and 7C which illustrate designsfor the ultrasonic element 112. FIG. 7A illustrates a series of shapeswhere the depth cross-section is rectangular as shown in element 132.The remaining elements in FIG. 7A are viewed from above. Element 134 isrectangular as seen from above. Element 136 is a hexagon. Element 138 isan irregular quadrilateral. Element 140 is a flattened circle. Element142 is a trapezium. Element 144 is a bullet shape. Element 146 is atrapezium having a shorter dimension between its parallel sides than thetrapezium of element 142. Element 148 is a comb shape having a narrowtooth at a first end followed by three wider teeth. Element 150 is a “W”shape, again with a narrow tooth projection at a first end.

FIG. 7B illustrates a closed ring shaped element 152 and an open ringshaped element 154.

FIG. 7C illustrates four variations on a cylindrical element. Element156 is a filled cylinder. Element 58 is a cylinder with a removablesector. Element 160 is a hollow cylinder having an opening 161 in thelower wall, and element 162 is a hollow cylinder having an open part ofthe cylinder wall along its length.

In addition the element 112 may be spherical.

In embodiments the transducer described above does not necessarilyinclude a focal point for the ultrasonic beam. As a result the beam canreach various targets without requiring a precise distance between theelement and the target, as will be described in greater detail below.

Possible construction of the transducer may comprise regular coatingmethods for piezo elements, and coating materials including one or moreof: silver, Ni, gold, copper, or carbon nano-tubes.

Additional coating of the electrodes may improve one or more of thefollowing: the electric conductivity, the acoustic matching, theacoustic reflection or the acoustic amplification.

The additional coating may use any of a variety of materials includingpolymers, glass and metals.

The PIEZO-electric material may for example comprise: PIEZO-electricceramics and/or PIEZO-electric quartz. An embodiment as discussedhereinbelow with cooling methods may allow the design to use highhardness ceramics, which have advantages of being of high efficiency,and being small and cheap.

MEMS—the acoustic element can also be implemented using MEMS.

More than one acoustic element can be implemented, for example:

a phased array matrix of elements;

a non-linear geometric array;

a matrix of elements each having different resonant frequencies

Reference is now made to FIGS. 8A and 8B which illustrate examples formulti-elements transducers. FIG. 8A is a side view showing fivepiezoelectric elements 170 mounted on a curved PCB 172. FIG. 8B is aview from above showing two rows of piezoelectric elements 174 and 176.

The housing 130 can made from one or more of the following materials:metals, ceramics, PZT, PIEZO-electric ceramics, glass, polymers orcarbons.

The housing may provide an angiogram directional projection for betterplacing of the element. The housing may further be shaped to providefocusing or to affect fluid flow within the lumen around the element.

The housing may be designed to provide relatively high heat transferfrom the element in order to avoid overheating. Typically the heatconductance is a function of shape and of the material used, howeverstandard cooling fins cannot be used in the blood stream as they maycause platelets to break, thus causing blood clots.

The housing can include acoustic damping materials, such as tungsten, oralternatively may be designed to provide an acoustic amplifying effect.As per the discussion above, typically some of the piezoelectric surfaceis damped and some is provided with acoustic amplification.

A drug delivery capsule may be provided to inject materials into thebloodstream as required by the procedure.

Reference is now made to FIG. 9, which illustrates an embodiment of aprinted circuit board 16 for mounting of the acoustic transducer 12. Theprinted circuit board may include different thickness to provide thegaps for the air pockets referred to above.

The printed circuit may comprise materials such as hard polymers,flexible polymers, glass-fiber and carbon fiber. Alternatively, theprinted circuit may be printed directly on the housing.

As discussed, connection to the acoustic element may use any of wiresoldering, paste soldering process, conductive gluing and wire bonding.The connection is preferably both a good heat conductor and a goodelectrical conductor.

The circuit itself may include vias of copper or other metals for higherheat transfer. One or more printed materials may be provided on theboard, including: copper, metals, polymers, and intermediate materials.

Coatings such as metals, PZT, chemical coatings, isolation coatings,hydrophilic coatings and hydrophobic coatings may be used on differentparts of the PCB or housing.

The acoustic transducer may be connected to the control unit 116 usingdifferent kinds of wires including: coax wire, twisted pair, and fiberoptic cable.

The acoustic transducer and the catheter may be coated with differentcoatings including: an isolation coating, a praline, NiSi, hydrophobiccoating, hydrophilic coating, or any kind of biocompatible coating,

As mentioned above, an air pocket may be maintained between the PCB andthe peizoelectric element.

The acoustic isolation of the piezoelectric element and consequentincrease in efficiency has been mentioned above. This advantage can beused for working in small cavities in order to improve the ability toheat the target volume without at the same time heating the transducervolume.

Air pockets may be formed by the use of trenches in the PCB structure asillustrated with reference to FIG. 9. or by providing a mounting asshown in FIG. 1 where a gap is defined between the ultrasonic elementand the PCB.

Hydrophobic coatings, including praline, may be used to enhance thesurface tension effect in order to prevent the water medium frompenetrating into the air volume, as mentioned in respect of FIG. 2.

The coating may cover the entire air bubble surrounding or part of itand prevent water from penetrating in.

It is noted that the air bubble does not need to be maintainedindefinitely. It is sufficient that it is retained for the duration ofthe ultrasound procedure.

The ultrasonic element may use different anti-resonance values for theworking frequency when available. For example one anti-resonance may beused for moderate heating of the tissue, another for power heating ofthe tissue and yet another for monitoring.

The device may be able to provide an injection jet to the tissue, mayprovide for increasing fluid flow under the element, say to improvecooling, may evoke micro-bubbles, and may monitor the heating effect andor any injection. The measurement system may include doppler analysisand the heat treatment may use focused or unfocused ultrasound.

In embodiments, the navigation unit 122 may allow the acoustic elementto reach the desired location. The navigation unit may further have someauxiliary functions. For example it may deliver the power to the elementfrom the control unit, record measurements from the element and evendeliver the measurements to the control unit 116. The navigation unitmay further be involved in heat absorption or transfer from thetransducer to the ambient or to the surrounding liquids by providing anadditional heat exchange surface extending from the catheter.

The navigation unit may also mechanically hold and place the ultrasonicelements in different locations and at different desired angles, as perFIG. 10. In FIG. 10 a ring configuration 180 may be used, or an angleconfiguration 182, or a cylindrical configuration 184 or a sideconfiguration 186 or a front configuration 188, each in relation to thecatheter.

In embodiments, the navigation unit may include an external navigatedcontrol unit. Close to the ultrasonic element, a placing unit mayinclude a balloon, a placing wire or a net or the like.

A heat sink function may including cooling the ultrasonic unit usingoutside fluid including: blood, urine or CSF. The function may includeincreasing the heat evacuation by pumping fluid over or from theacoustic unit surface. The function may involve increasing the heatevacuation using internal or external heat conductive material,including: blood passivation coating, or printed coating, or may includeincreasing the heat evacuation using an internal or external heatconductive balloon.

Heat evacuation may be increased by using an internal or external heatconductive balloon with heat conduction material.

The control unit 116 may provide various kinds of closed loop controland indications on the treatments. The control unit may receive signalsfrom echoes from the tissue. The echo may indicate the area andtreatment effect, or the echo can indicate the distance from the cavitywall to the transducer device. The sensor may be a temperature sensor,which may indirectly sense the temperature of the transducer bymeasuring fluid that has just passed the sensor. The temperature mayindicate the treatment efficiency, or efficiency of cooling of thecavity, or the cooling or heating of the transducer.

A power sensor can indicate the output treatment energy. A bloodpressure sensor or other like sensors may be provided to indicatereaction to the treatment. A flow sensor can monitor fluid flow in theregion of the treatment.

Closed loop effects which do not require the control unit may also beused, as known to the skilled person, for example a coating material onthe transducer surface may be provided that attaches to particles orother materials that come from the treated tissue. The attachment may beused to control the ultrasonic process by making changes to thetransducer frequency during operation.

Materials that can be inserted into the target tissue volume includerestenosis prevention materials, for treatment of blood vessels, andmaterials that are used in drug eluting stents, such as sirolimus, andpaclitaxel.

Other materials can be used, say in drug exuding balloons, and mayinclude materials that are used for bio-degradable stents,anti-Inflammatory materials, medications that may be better presentedlocally to the tissue than systemically, anti-thrombotic materials, suchas Heparin, Aspirin, Ticlopidine, and Clopidogrel, and materials thatcan cause damage or death to target tissues. Thus materials that cancause nerve death may be supplied for renal denervation.

Also, materials that may help in blocking of the tissuemicro-circulation in heating, such as polymers that undergo crosslinking, or soluble collagen, or material that may increase theultrasonic heating of the tissue, such as micro-bubbles that causehigher energy absorption, may be used, or in the latter case generatedon site.

Micro-bubble transportation through the cells membrane can be increasedusing the acoustic treatment, and achieve a multiplicative effect.

Also any kind of medication can be applied.

The transducer may be positioned on a catheter inside blood-vessels orblood cavities. Ultrasonic irradiation of the target tissue from insidethe vessel lumen or cavity outwards may then be provided. Cooling of thepiezoelectric element may be achieved by making the design sufficientlyconductive and then using blood flow or flow of a fluid from an externalsource, such as saline that is irrigated into the blood vessel.

The transducer may be positioned on a catheter inside tissue canals orcavities of body fluids in the body, such as the urethra or urinarybladder, or in the spinal cord or brain ventricles (CNS fluid).Ultrasonic irradiation of the target tissue from inside the canal/cavityoutwards may then be provided.

The transducer may alternatively be positioned on the tip of anendoscope or like device. The endoscope is inserted through a small holein the skin, and the ultrasonic transducer is positioned on or near thetarget tissue.

For cooling, external irrigation is allowed to flow into the area of thetreatment cavity. The endoscope tip may for example be positioned insidea balloon like device. The cooling fluid flows inside the balloon. Theballoon is positioned next to the treatment tissue location. Theultrasonic transducer irradiates the target tissue through the balloonwall. Alternatively, the balloon may be positioned on the skin and notinserted through it. The treatment target may be near the skin.

The ultrasonic transducer may be positioned at a location that allowsultrasonic irradiation of the target tissue. Irrigation of requiredmaterial in a liquid form may be provided into the blood vessels orlymphatic vessels that supply the perfusion or lymphatic capillaries ofthe target tissue volume, for example the artery vasa-vasorum.

The method may involve waiting a known time constant for the requiredmaterial to reach the target tissue.

It is possible to add micro-bubbles to the fluid material in order tohelp with detection of presence of the material in the target tissue.Micro-bubbles may be detected using ultrasound and sub-harmonic imaging.Micro-bubbles may also improve heating of the target tissue underultrasonic energy, due to higher absorption of the ultrasonic energy inthe tissue volume where they are located.

Applying a thermal effect in the tissue may cause the capillaries to beblocked mechanically or by blood coagulation.

Ultrasound energy applies mechanical force on particles that are presentin a liquid, when there is a difference in the acoustic impedance, whichis a function of the density multiplied by the speed of sound, betweenthe particles and the liquid. The applied force then pushes particlesalong the direction of the traveling ultrasonic waves. The mechanicalforce phenomenon can be used to ensure that required substances arriveat the treatment site.

The ultrasonic transducer may be positioned in a tissue liquid cavitysuch as a blood vessel, near the target tissue, while ensuring a liquidspacing between the target tissue and the ultrasonic transducerirradiating face. As mentioned above a control loop can be used toensure that the transducer does not touch the vessel wall and damageepithelium cells.

The required material may be released into the tissue liquid cavity in away that will cause some of the particles to enter the spacing betweenthe target tissue and the ultrasonic transducer irradiating face. Oneway of doing this is to coat the face of the ultrasonic transducer withthe required material, such that the operation of the ultrasonictransducer may cause particles of the required material to be releasedinto the surrounding liquid.

Another possibility is to add micro-bubbles to the required materialfluid in order to detect the material presence in the target tissue.Micro-bubbles may be detected using ultrasound and sub-harmonic imaging.

Yet another possibility is to activate the ultrasonic transducer so asto apply force on the required material particles to push the particlesinto the blood vessel wall near the ultrasonic transducer irradiatingface, using the pushing effect mentioned above.

Another possibility is to apply the ultrasonic energy in short highpower pulses with long separations between each pulse. This may applymechanical force, as per the phenomenon discussed above, to theparticles to push them into the tissue wall, without heating the tissuewall extensively.

A further possibility is that activation of the captured requiredmaterial can be achieved by applying additional ultrasonic energy orsome other kind of external energy such as a magnetic field onFerro-electric particles, or an ultrasonic shock-wave to the particles

The present embodiments may be used for the treatment of renaldenervation. The transducer is simply positioned at 1, 2 or moretreatment points, and there is no need for tip manipulation or accuratepositioning. The total energizing duration may be between two secondsand two minutes. Real-time feedback of treatment progress may beprovided. The advantages of ultrasonic treatment include directional,localized and remote target tissue effects with minimal damage to othercloser tissues, possibly reducing pain, preservation of endothelium andelastic lamina structure and function, sot that there is no posttreatment stenosis, or at least reduced post treatment stenosis, theavoidance of any mechanical contact on the blood vessel wall, andoverall a more robust treatment effect due to real-time feedback.

The following table is a summary of currently contemplated clinicalapplications.

TABLE 1 Currently Contemplated Clinical Applications # Application NameAnatomy Target 1. Renal sympathetic nerve Renal artery Renal sympatheticnerves modulation 2. Carotid sympathetic nerve Carotid artery Carotidsympathetic nerves modulation 3. Vagus sympathetic nerve Aorta Vagussympathetic nerve modulation 4. Peripheral sympathetic nerve Peripheralblood Peripheral sympathetic nerves modulation vessels 5. Pain nervemodulation Spinal cord cannel Pain nerves 6. Restenosis decrease Allrelevant arteries Artery media and adventitia 7. Vulnerable plaque Allrelevant arteries Artery media and adventitia stabilization 8.Atherosclerosis All relevant arteries Artery media and adventitiapassivation 9. Plaque volume All relevant arteries Artery media andadventitia decrease 10. Plaque thrombosis All relevant arteries Arterymedia and adventitia decrease 11. Tetanic limb muscle Limb arteries orveins Peripheral motor nerves tonus decrease 12. Atrial fibrillationRight atria Pulmonary vain insertion prevention 13. Cardiac arrhythmiaCoronary arteries Cardiac tissue pathology prevention 14. Liver tumornecrosis Inferior vena cava Tumor 15. None-malignant Urethra Sickprostate tissue prostate treatment 16. Malignant prostate Urethra Sickprostate tissue treatment 17. Artery aneurysms All relevant arteriesAneurysm wall stabilization 18. Aortic aneurysms Aorta Aneurysm wallstabilization 19. Berry aneurysms Brain arteries Aneurysm wall sealing20. Erectile dysfunction Internal Iliac Artery media and adventitiatreatment

Table 2 below summarizes embodiments of the technology and uses.

TABLE 2 Summary of Technology 1. Technology 1.1. The ultrasonictransducer: 1.1.1. Very small: 1.5 × 8 [mm] 1.1.2. Very thin: 0.8 [mm]1.1.3. Very high ultrasonic intensity output: 100 [W/cm{circumflex over( )}2] continuous 1.1.4. Relatively high work frequencies: 10-25 [MHz].1.1.5. Biocompatible coating: Perylene 1.2. The catheter 1.2.1.Ultrasonic transducer cooling: vessel blood/liquid flow + catheterbreading as heat sink 1.2.2. Very flexible treatment tip: 10 mm stifflength. (Pass through 8Fr “hokey-stick” guide catheter) 1.2.3. Preciseand easy torque following 1.2.4. Standard 0.014 OTW 1.2.5. Relativelysmall diameter: 6 Fr 1.3. Distancing fixture 1.3.1. Distancingtransducer face from artery wall to prevent contact damage, with minimalmechanical forces on artery wall 2. Technology functionality 2.1.Non-focused ultrasonic beam-like ultrasonic emission 2.1.1. Simpleanatomic 2.1.2. Big treatment volume cross-section, the size of thetransducer face (differing from focused ultrasound with small treatmentvolume) 2.1.3. Relatively even spread of ultrasonic energy in beamcross-section (No need to precise anatomic positioning like in focusedultrasound) 2.2. Treatment maneuverability and directionality 2.2.1.Simple maneuvering with nearly 1:1 torquability. 2.2.2. Simple treatmentbeam directivity feedback and control from standard angiograph (0, 90,180, 270) 2.2.3. No need for high operator skills 2.2.4. No problem touse contrast agent during treatment 2.3. Ultrasonic imaging using theunique transducer - Continuous measurement of distance to artery wall2.3.1. Treatment tip real positioning measurement (not possible onlyfrom angiography) 2.3.2. Feedback to prevent high power operation of thetransducer while touching the artery wall. 3. Tissue treatment 3.1. Veryfast treatment: 3.1.1. Treatment duration of 30-5 sec per treatmentpoint. 3.1.2. Possibly 4 treatment point per artery for renaldenervation 3.2. Remote and localized effect 3.2.1. Thermal effectvolume in the tissue far from the transducer face: media, adventitia,Vasa-Vasorum, peri-adventitia, adventitia nerves, peri- adventitianerves, peri-adventitia capillaries. 3.2.2. Targeting tissues in varyingdistances from transducer face according to treatment parameters (notpossible in most focused ultrasonic catheter designs) 3.2.3. Possibilityto apply thermal effect in tissues located 5 mm from the lumen wall.Relevant for peripheral nerves blocking from peripheral arteries. 3.2.4.Non targeted tissues on the beam path to the target tissue are notdamaged. 3.2.5. Importantly no damage to the endothelium, basal membraneand internal elastic lamina. 3.3. Tissue selectivity 3.3.1. Highlyselective remote thermal effect in nerve bundles that are covered withthick fat tissue. (most relevant to Renal Denervation in the Renalartery ostium) 3.4. Treatment special features for Renal Denervation3.4.1. Working very close to artery ostium: <10 [mm] 3.4.2. Working inshort arteries: <20 [mm] 3.4.3. Working in small arteries: 4-3 [mm] 4.Safety 4.1. The temperature of the blood that flows over the ultrasonictransducer does not go over 50 C. while working in the maximal allowedoperation intensity level 50 [W/cm{circumflex over ( )}2]. 4.2. Thetemperature of the blood that flows over the ultrasonic transducer doesnot go over 43 C. while working in the therapeutic operation intensitylevel 30 [W/cm{circumflex over ( )}2]. No need to add external coolingsaline injection. 4.3. The therapeutic treatment on the blood vesselwall is done with no mechanical contact with the vessel wall. No dangerof damaging the vessel wall or disrupting any pathologies on the wall(Atherosclerosis plaques) 4.4. Localized and controlled effectspecifically in the targeted treatment volume. No non-controlled energyeffects in other tissues (unlike in RF treatment). 4.5. No blocking ofthe blood flow during the treatment 5. Possible implications 5.1. Muchless pain in treatment: fast blocking of nerves with no electricexcitation of the target nerve and no effect on other nerves (Incontrast with Unipolar RF treatment)

Reference is now made to FIGS. 11-16 which illustrate experimentalresults following use of the device.

FIG. 11 is a histology slide, using H&E stain, and showing the thermaleffect in a pig carotid artery. The border of the thermal effect regionin the tissue is marked with a dashed line and noted as “ThermalDamage”. The setup used was an ultrasonic catheter from inside the bloodvessel.

FIG. 12 is a histology slide, using H&E stain, and showing the thermaleffect in a pig renal artery. The border of the thermal effect region inthe tissue is marked with a dashed line and noted as “Thermal”. Anecrotic nerve inside the thermal effect region is marked with an arrowand “necrotic nerve” text. The setup involved an ultrasonic catheterfrom inside the blood vessel.

It is noted that the embodiments cause thermal damage in target tissuesfar from the lumen internal wall, while causing no thermal damage in thelumen wall internal layer.

Specifically in blood vessels it was shown that thermal damage wasachieved in the adventitia or media layers, without causing any apparentdamage in the intima layer, either the endothelium or the elasticlamina.

It is believed that the reason for this effect is that the ultrasonicenergy heats the artery wall all along the beam, but the blood flow inthe lumen cools the tissue that is close to the blood flow, thus theendothelium wall never heats sufficiently to be damaged. It is possibleto find a setting for the treatment parameters so to cause heating above55 C of the tissues far from the blood flow, while the temperature ofthe intima layer is kept below 55 C.

Exemplary results are shown in FIGS. 13 and 14 which are histologyslides wherein analysis and marking of the thermal damage area to a pigCarotid Artery and a Pig Renal Artery respectively, is made by a trainedpathologist.

Heating the adventitia or media can cause blocking of the flow insidethe small capillaries (called Vasa-Vasorum) in the blood vessel mediaand adventitia, for example by mechanical crimping due to the shrinkingof the connective tissue due to collagen denaturation, or due tothrombotic blocking by a thrombus that is formed in the Vasa-Vasorumbecause of the thermal damage (the blood flow in these vessels is verylow so it can not cool the blood vessel).

FIG. 15 illustrates exemplary results for the above. A histology slideshows analysis and marking of the blocked Vasa-Vasorum with arrowsplaced by a trained pathologist in a pig Carotid Artery Vasa-Vasorum inthe adventitia.

The treatment is intended to provide extensive thermal damage tospecific target tissues while keeping nearby tissues undamaged.

It is believed that the ultrasonic energy absorption is different fordifferent kinds of tissue and, and furthermore, the content of collagenfibers may differ.

Specifically it was shown that in nerve fibers that are wrapped by fattissue, it is possible to cause extensive thermal damage to the nervetissue, while there is no significant thermal damage in the fat tissueor/and to the tissue surrounding them.

FIG. 16 illustrates two histology slides with analysis and marking ofthe thermal damage, or nerve degeneration area made by a trainedpathologist, for a pig renal artery, and nerves in adventitia.

It is appreciated that certain features of the invention, which are, forclarity, described in the context of separate embodiments, may also beprovided in combination in a single embodiment. Conversely, variousfeatures of the invention, which are, for brevity, described in thecontext of a single embodiment, may also be provided separately or inany suitable subcombination.

Although the invention has been described in conjunction with specificembodiments thereof, it is evident that many alternatives, modificationsand variations will be apparent to those skilled in the art.Accordingly, it is intended to embrace all such alternatives,modifications and variations that fall within the spirit and broad scopeof the appended claims. All publications, patents, and patentapplications mentioned in this specification are herein incorporated intheir entirety by reference into the specification, to the same extentas if each individual publication, patent or patent application wasspecifically and individually indicated to be incorporated herein byreference. In addition, citation or identification of any reference inthis application shall not be construed as an admission that suchreference is available as prior art to the present invention.

What is claimed is:
 1. A method for controlling a treatment effect onblood vessel tissue during a non-focused ultrasonic treatment,comprising positioning a non-focused ultrasonic transducer device whichgenerates one or more non-focused ultrasonic beams with frequency in arange of 8 MHz-30 MHz for generating a treatment effect in target tissueoutside of the inner wall of said blood vessel, said device positionedin the blood vessel lumen in a manner which prevents contact of saidtransducer with the inner wall, wherein said transducer faces saidtarget tissue; controlling said treatment effect by controlling fluidflow, wherein said controlling comprises deploying a fluid restrictor ata location relative to said transducer effective to block at least aportion of fluid flowing upstream, downstream or adjacent saidtransducer; and wherein said deployed fluid restrictor allows naturalblood flow between said transducer and said inner wall of said bloodvessel to cool said inner wall.
 2. The method according to claim 1,wherein said fluid is blood.
 3. The method according to claim 1, whereinsaid restrictor is deployed to block the flow upstream relative to saidtransducer device to load the vasa vasorum with a liquid material. 4.The method according to claim 3, wherein said liquid material comprisesmicro bubbles to increase energy absorption in the target tissue.
 5. Themethod according to claim 1, wherein said restrictor is deployed toblock the flow downstream relative to said transducer device to allowdrug delivery to target tissue areas treated by said transducer device.6. The method according to claim 5, wherein said drug is one or more of:restenosis prevention drug, anti-inflammatory drug, anti-thromboticdrug.
 7. The method according to claim 1, wherein said deployingcomprises inflating a balloon.
 8. The method according to claim 1,wherein said fluid is a cooling fluid effective to cool said transducerdevice.
 9. The method according to claim 1, wherein said deployingcomprises ensuring a fluid spacing between an irradiation face of saidultrasonic transducer device and target tissue.
 10. The method accordingto claim 1, wherein said treatment effect comprises cell necrosis. 11.The method according to claim 1, further comprising estimating saidtreatment effect according to an echo received on said transducer. 12.The method according to claim 1, wherein said controlling said treatmenteffect comprises controlling fluid flow according to real-time feedbackfrom the tissue.
 13. The method according to claim 1, wherein said fluidrestrictor blocks only a portion of fluid flowing downstream saidtransducer.
 14. The method according to claim 13, wherein a portion ofsaid fluid flowing downstream which is not blocked by said fluidrestrictor comprises said natural blood flow.
 15. The method accordingto claim 1, wherein said deployed fluid restrictor is in the form of awire or a thin plastic sheet.
 16. The method according to claim 1,wherein said fluid restrictor is deployed at a location around saidnon-focused ultrasonic transducer device and allows natural blood flowon said non-focused ultrasonic transducer device outer surface.
 17. Themethod according to claim 1, wherein said non-focused ultrasonictransducer device is positioned at a distance from said inner wall ofsaid blood vessel when generating said treatment effect whilemechanically ensuring a liquid space between said inner wall and saidtransducer.
 18. The method according to claim 1, wherein saidnon-focused ultrasonic transducer device is flat.
 19. The methodaccording to claim 1, further comprising treating said target by saidone or more non-focused ultrasonic beams without affecting said innerwall of said blood vessel, and wherein said controlling comprisingcontrolling fluid flow in said blood vessel during said treating. 20.The method according to claim 19, wherein said target tissue is locatedat least 5 mm from said blood vessel lumen.
 21. The method according toanyone of claim 19 or 20, wherein said target tissue comprises nervetissue which resides outside of said blood vessel wall.
 22. The methodaccording to claim 1, wherein said frequency is in the range of 10MHz-30 MHz.
 23. The method according to claim 1, wherein said fluidrestrictor is effective to block a portion of said fluid which is largeenough so as to change said treatment effect.
 24. The method accordingto claim 1, wherein said inner wall of said blood vessel comprises theintima, and said target tissue comprises at least one of the media andadventitia of said blood vessel.
 25. A non-focused ultrasonic transducerdevice comprising: a non-focused flat piezoelectric transducerconfigured to generate one or more non-focused ultrasonic beams andsized for placement in a body lumen in which blood naturally flows,wherein said piezoelectric transducer is configured to be placed in saidbody lumen in a manner which prevents contact of said piezoelectrictransducer with the inner wall of said body lumen, wherein saidtransducer faces target tissue located outside of the inner wall of saidbody lumen; a controller which electrifies said piezoelectric transducerto generate a non-focused ultrasonic power beam with frequency in arange of 8 MHz-30 MHz, total energy and for a time period suitable fortreating said target tissue; a power unit enabling said ultrasonic powerbeam for tissue ablation; and a fluid restrictor effective to block atleast a portion of fluid flowing upstream, downstream, or adjacent saidpiezoelectric transducer; wherein said fluid restrictor, when deployed,is shaped and positioned to allow at least some of said natural flow ofblood between said transducer and said inner wall of said body lumen tocool said inner wall enough to prevent thermal damage to said innerwall.
 26. The device according to claim 25, wherein said fluidrestrictor is a balloon.
 27. The device according to claim 25, whereinsaid fluid restrictor is a wire, a net, or a thin sheet.
 28. The deviceaccording to claim 25, wherein said device further comprises a controlunit configured to activate deployment of said fluid restrictor.
 29. Thedevice according to claim 28, wherein said device further comprises aflow sensor, and said control unit is configured to monitor fluid flowin the region of treatment based on an indication from said flow sensor.30. The device according to claim 25, further comprising a perfusionunit configured for ejecting substances into the vessel.
 31. The deviceaccording to claim 25, wherein said fluid restrictor serves as a placingelement for positioning said transducer in the vessel.
 32. The deviceaccording to claim 25, wherein said device further comprises atemperature sensor and said fluid restrictor is positioned to allow thesensor to detect a temperature of fluid flowing passed said transducer.33. The device according to claim 25, wherein said piezoelectrictransducer is protected by a housing, said housing shaped to affectfluid flow within a lumen around said piezoelectric transducer.
 34. Thedevice according to claim 25, wherein said fluid restrictor blocks onlya portion of fluid flowing downstream said transducer to allow for atleast some of said natural flow of blood between said transducer and aninner wall of said body lumen.
 35. The device according to claim 25,wherein said fluid restrictor is shaped and positioned to (1) restrictblood flow on said non-focused flat piezoelectric transducer, and to (2)prevent contact of said non-focused flat piezoelectric transducer withsaid inner wall of said body lumen.
 36. The device according to claim25, wherein said frequency is in the range of 10 MHz-30 MHz.
 37. Amethod for controlling a treatment effect on blood vessel tissue duringan ultrasonic treatment, comprising positioning an ultrasonic transducerdevice in the blood vessel lumen, wherein said transducer faces targettissue located outside of an inner wall of said blood vessel; treatingsaid target tissue by one or more non-focused ultrasonic beams with afrequency in a range of 10 MHz-30 MHz for generating a treatment effect,generated by said ultrasonic transducer without damaging a surface ofsaid inner wall; controlling a treatment effect by controlling fluidflow, wherein said controlling comprises deploying a fluid restrictor inthe form of a wire or a thin plastic sheet, at a location relative tosaid transducer effective to block at least a portion of fluid flowingupstream, downstream or adjacent said transducer; wherein said deployedfluid restrictor allows natural blood flow between said transducer andsaid inner wall of said blood vessel to cool said innerwall; andmonitoring said fluid flow using a flow sensor.
 38. A method forcontrolling a treatment effect on blood vessel tissue during anultrasonic treatment, comprising positioning an ultrasonic transducerdevice in the blood vessel lumen, wherein said transducer faces targettissue located outside of an inner wall of said blood vessel; treatingsaid target tissue by one or more non-focused ultrasonic beams with afrequency in a range of 10 MHz-30 MHz for generating a treatment effect,generated by said ultrasonic transducer without damaging a surface ofsaid inner wall; and controlling a treatment effect by controlling fluidflow, wherein said controlling comprises deploying a fluid restrictor ata location around said transducer effective to block at least a portionof fluid flowing upstream, downstream or adjacent said transducer; andwherein said deployed fluid restrictor allows natural blood flow betweensaid transducer and said inner wall of said blood vessel to cool saidinner wall.
 39. A method for controlling a treatment effect on bloodvessel tissue during an ultrasonic treatment, comprising positioning anon-focused ultrasonic transducer device in the blood vessel lumen, at adistance from an inner wall of said blood vessel, wherein saidtransducer faces target tissue outside of said inner wall of said bloodvessel, while mechanically ensuring a liquid space between said innerwall and said non-focused ultrasonic transducer device; treating saidtarget tissue by one or more non-focused ultrasonic beams with afrequency in a range of 10 MHz-30 MHz generated by said non-focusedultrasonic transducer without damaging a surface of said inner wall; andcontrolling a treatment effect by controlling fluid flow, wherein saidcontrolling comprises deploying a fluid restrictor at a locationrelative to said transducer effective to block at least a portion offluid flowing upstream, downstream or adjacent said transducer; andwherein said deployed fluid restrictor allows natural blood flow betweensaid transducer and said inner wall of said blood vessel to cool saidinner wall.